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Team Discovers Antigen That Blocks Transmission of a Deadly Malaria Parasite in the Midgut of a Mosquito

photo of a mosquito
Mosquito Anopheles gambiae.
Credit: CDC

Marcelo Jacobs-Lorena, Ph.D., research seeks to increase the understanding of how the malaria parasite, Plasmodium, interacts with its primary mosquito host, Anopheles gambiae.

A novel finding by his research group at the W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, supported by NIAID, may constitute the basis for a future “universal” malaria vaccine. Dr. Jacobs-Lorena and his colleagues identified a previously unknown mosquito antigen that the parasite uses for entry into the mosquito midgut, a critical step in the parasite’s development. Mosquitoes pick up Plasmodium from infected hosts during a blood feeding. Before those malaria parasites can be transmitted to a new human host, they must first penetrate the mosquito midgut. This penetration requires recognition of the antigen, called Anopheles gambiae aminopeptidase N (AgAPN1), on the surface of the mosquito midgut. Dr. Jacobs-Lorena team produced an antibody that acts as a blanket that prevents the parasite from accessing the mosquito midgut antigen.

Vaccines based on this antigen have the potential to block transmission of the deadliest human malaria parasite, P. falciparum, in a broad range of mosquito species, including Anopheles gambiae, Anopheles stephensi, and possibly most parasite vectors. The researchers also have preliminary data showing that the antibody can block another human malaria parasite, Plasmodium vivax.

In other NIAID-funded work, Dr. Jacobs-Lorena and his team created genetically modified mosquitoes resistant to Plasmodium. This finding raises the possibility of one day stopping the spread of the disease. The research team combined equal numbers of genetically engineered and natural mosquitoes in the laboratory and let them feed on malaria-infected mice. The genetically engineered mosquitoes outbred natural mosquitoes, raising the possibility that they might be able to replace them if released into the wild. The study suggests that when feeding on malaria-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over non-transgenic mosquitoes. The lab-altered mosquitoes competed equally well with natural insects when fed non-infected blood but did not outbreed their natural counterparts in that case.

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Last Updated June 17, 2009